scholarly journals Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2-1

2019 ◽  
Vol 116 (41) ◽  
pp. 20545-20555 ◽  
Author(s):  
Danielle R. Little ◽  
Kamryn N. Gerner-Mauro ◽  
Per Flodby ◽  
Edward D. Crandall ◽  
Zea Borok ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
3D Imaging ◽  
Blood Stream ◽  
Alveolar Type ◽  
Genomic Profiling ◽  
Rna Seq ◽  
Cell Type ◽  
Cellular Quiescence ◽  
Exchange Surface

The extraordinarily thin alveolar type 1 (AT1) cell constitutes nearly the entire gas exchange surface and allows passive diffusion of oxygen into the blood stream. Despite such an essential role, the transcriptional network controlling AT1 cells remains unclear. Using cell-specific knockout mouse models, genomic profiling, and 3D imaging, we found that NK homeobox 2-1 (Nkx2-1) is expressed in AT1 cells and is required for the development and maintenance of AT1 cells. Without Nkx2-1, developing AT1 cells lose 3 defining features—molecular markers, expansive morphology, and cellular quiescence—leading to alveolar simplification and lethality. NKX2-1 is also cell-autonomously required for the same 3 defining features in mature AT1 cells. Intriguingly, Nkx2-1 mutant AT1 cells activate gastrointestinal (GI) genes and form dense microvilli-like structures apically. Single-cell RNA-seq supports a linear transformation of Nkx2-1 mutant AT1 cells toward a GI fate. Whole lung ChIP-seq shows NKX2-1 binding to 68% of genes that are down-regulated upon Nkx2-1 deletion, including 93% of known AT1 genes, but near-background binding to up-regulated genes. Our results place NKX2-1 at the top of the AT1 cell transcriptional hierarchy and demonstrate remarkable plasticity of an otherwise terminally differentiated cell type.

scholarly journals Epithelial Vegfa specifies a distinct endothelial population in the mouse lung

2019 ◽  
Author(s):  
Lisandra Vila Ellis ◽  
Margo P Cain ◽  
Vera Hutchison ◽  
Per Flodby ◽  
Edward D Crandall ◽  
...  
Keyword(s):  
Mouse Lung ◽  
Alveolar Type ◽  
Vascular Endothelial ◽  
Rna Seq ◽  
Alveolar Space ◽  
Normal Appearance ◽  
Endothelial Growth Factor ◽  
Shed Light

SUMMARYThe lung microvasculature is essential for gas exchange and commonly considered homogeneous. We show that Vascular endothelial growth factor A (Vegfa) from the epithelium specifies a distinct endothelial cell (EC) population in the postnatal mouse lung. Vegfa is predominantly expressed by alveolar type 1 (AT1) cells and locally required to specify a subset of ECs. Single cell RNA-seq identified 15-20% lung ECs as transcriptionally distinct and marked by Carbonic anhydrase 4 (Car4), which are specifically lost upon epithelial Vegfa deletion. Car4 ECs, unlike bulk ECs, have extensive cellular projections and are separated from AT1 cells by a limited basement membrane without intervening pericytes. Without Car4 ECs, the alveolar space is aberrantly enlarged despite the normal appearance of myofibroblasts. Lung Car4 ECs and retina tip ECs have common and distinct transcriptional profiles. These findings support a signaling role of AT1 cells and shed light on alveologenesis.

scholarly journals Evaluation of Cell Type Annotation R Packages on Single-cell RNA-seq Data

2020 ◽  
Author(s):  
Qianhui Huang ◽  
Yu Liu ◽  
Yuheng Du ◽  
Lana X. Garmire
Keyword(s):  
Single Cell ◽  
Rna Seq ◽  
Cell Type ◽  
R Packages

scholarly journals T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

Immunology ◽  
2008 ◽  
Vol 125 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Chris J. Hedegaard ◽  
Martin Krakauer ◽  
Klaus Bendtzen ◽  
Henrik Lund ◽  
Finn Sellebjerg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
T Helper Cell ◽  
Helper Cell ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type

Cell type diversity in scallop adductor muscles revealed by single-cell RNA-Seq

Genomics ◽  
2021 ◽  
Vol 113 (6) ◽  
pp. 3582-3598
Author(s):  
Xiujun Sun ◽  
Li Li ◽  
Biao Wu ◽  
Jianlong Ge ◽  
Yanxin Zheng ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Seq ◽  
Cell Type ◽  
Adductor Muscles

Profile of podocyte translatome during development of type 2 and type 1 diabetic nephropathy using podocyte-specific TRAP mRNA RNA-seq

Diabetes ◽  
2021 ◽  
pp. db210110
Author(s):  
Yinqiu Wang ◽  
Aolei Niu ◽  
Yu Pan ◽  
Shirong Cao ◽  
Andrew S. Terker ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Rna Seq

scholarly journals Breast cancer risk and germline genomic profiling of women with neurofibromatosis type 1 who developed breast cancer

2017 ◽  
Vol 57 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Xia Wang ◽  
Jamie K. Teer ◽  
Renee N. Tousignant ◽  
Albert M. Levin ◽  
David Boulware ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Genomic Profiling

scholarly journals RNA Sequencing (RNA-Seq) Based Transcriptome Analysis in Immune Response of Holstein Cattle to Killed Vaccine against Bovine Viral Diarrhea Virus Type I

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 344 ◽  
Author(s):  
Bryan Irvine Lopez ◽  
Kier Gumangan Santiago ◽  
Donghui Lee ◽  
Seungmin Ha ◽  
Kangseok Seo
Keyword(s):  
Immune Response ◽  
Enrichment Analysis ◽  
Receptor Interaction ◽  
Type I ◽  
Rna Seq ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Kegg Pathways ◽  
Viral Diarrhea Virus

Immune response of 107 vaccinated Holstein cattle was initially obtained prior to the ELISA test. Five cattle with high and low bovine viral diarrhea virus (BVDV) type I antibody were identified as the final experimental animals. Blood samples from these animals were then utilized to determine significant differentially expressed genes (DEGs) using the RNA-seq transcriptome analysis and enrichment analysis. Our analysis identified 261 DEGs in cattle identified as experimental animals. Functional enrichment analysis in gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed the DEGs potentially induced by the inactivated BVDV type I vaccine, and might be responsible for the host immune responses. Our findings suggested that inactivated vaccine induced upregulation of genes involved in different GO annotations, including antigen processing and presentation of peptide antigen (via MHC class I), immune response, and positive regulation of interferon-gamma production. The observed downregulation of other genes involved in immune response might be due to inhibition of toll-like receptors (TLRs) by the upregulation of the Bcl-3 gene. Meanwhile, the result of KEGG pathways revealed that the majority of DEGs were upregulated and enriched to different pathways, including cytokine-cytokine receptor interaction, platelet activation, extracellular matrix (ECM) receptor interaction, hematopoietic cell lineage, and ATP-binding cassette (ABC) transporters. These significant pathways supported our initial findings and are known to play a vital role in shaping adaptive immunity against BVDV type 1. In addition, type 1 diabetes mellitus pathways tended to be significantly enriched. Thus, further studies are needed to investigate the prevalence of type 1 diabetes mellitus in cattle vaccinated with inactivated and live BVDV vaccine.

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